Modified Project Summary/Abstract Section Chronic low back pain (CLBP) is a major public health concern. Complementary/integrative (C/I) chronic pain interventions have proliferated (eg, Mindfulness Training [MT], spinal manipulation therapy [SMT]), and some approaches have strong support for efficacy. Most research has focused on questions regarding treatment efficacy. However, important questions regarding treatment mechanisms have been neglected. A parsimonious approach to uncovering C/I treatment mechanisms may start from the hypothesis that C/I treatments work to a large extent via non-specific mechanisms that may be shared across treatments. Candidate non-specific mechanisms can be grouped into at least 3 categories: endogenous pain inhibitory systems (endogenous opioid function; conditioned pain modulation), pain-related cognition (pain catastrophizing; self-efficacy), and therapy factors (therapeutic relationship, patient expectations). The general hypothesis is that treatment-induced changes in these non-specific mechanisms will predict outcomes across different C/I interventions. At the same time, the contribution of specific mechanisms must be addressed. For MT, this would be changes in mindfulness, whereas for SMT, this would be changes in spinal stiffness. The proposed study will compare the degree to which MT and SMT activate specific and non-specific mechanisms, and the degree to which these mechanisms affect pain-related outcomes. Comparing the activation and effects of mechanisms in these 2 interventions in a single trial will allow us to test the degree to which effects of certain mechanisms are shared across treatments or are unique to a given treatment. 240 people with CLBP will be randomly assigned to MT, or SMT. All mechanism and outcome measures will be assessed frequently across all treatments. We expect the 2 treatments to produce significant changes in pain, mood and function. Aim 1 will test to what degree MT and SMT produce changes in non-specific mechanisms. Aim 2 will test to what degree MT and SMT produce changes in treatment-specific mechanisms (MT: mindfulness; SMT: spinal stiffness). Aim 3 will test to what degree changes in non-specific and specific mechanisms predict changes in pain, mood and function, and whether these relationships depend on the treatment received, and the degree to which changes in non-specific and specific mechanisms account for unique and shared variance in predicting outcomes. Addressing questions of mechanism is critical to the science and practice of C/I pain interventions because it: (1) tests theory validity, (2) provides empirically-supported rationale for asking people with pain to devote the resources needed to participate in treatment, (3) identifies the effective mechanisms of pain treatments and reveals those that may be redundant or inert, and (4) provides theoretical and empirical principles by which to enhance those C/I mechanisms that are most closely linked to the largest benefits.